Distinct behavioral phenotypes in male mice lacking the thyroid hormone receptor α1 or β isoforms.
Distinct behavioral phenotypes in male mice lacking the thyroid hormone receptor α1 or β isoforms.
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DOI：
10.1016/j.yhbeh.2013.03.015
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发表时间：
2013-05
影响因子：
3.5
通讯作者：
Ogawa, Sonoko
中科院分区：
文献类型：
--
作者：
Vasudevan, Nandini;Morgan, Maria;Pfaff, Donald;Ogawa, Sonoko
甲状腺激素通过甲状腺激素受体（TRs）影响神经元发育和焦虑。TR由两个不同的基因TRα和TRβ编码。TRα1的缺失与雄性焦虑增加有关，可能通过海马GABA能活性增加。我们比较了性腺完整的TRα1敲除（α1KO）和TRβ（βKO）雄性小鼠与野生型小鼠的社会行为和两种潜在的相关非社会行为，即状态焦虑和对听觉和触觉惊吓的反应。我们首次显示了两种TR亚型TRα1和TRβ在状态焦虑调节中的相反作用，与相应的野生型小鼠相比，α1敲除动物（α1KO）表现出更高的焦虑水平，而βKO雄性表现出更少的焦虑。与非社会环境中焦虑增加不一致的是，α1KO男性对听觉和触觉惊吓刺激的反应水平也较低。与T4抑制雌性小鼠脊柱前凸的数据一致，我们发现α1KO雄性小鼠的性行为轻微增加。这些行为支持TRα1可能抑制ERα驱动的转录，最终影响ERα驱动的行为，如脊柱前凸。行为表型指出TRs的新角色，特别是在非社会行为中，如状态焦虑和惊吓。
Thyroid hormones influence both neuronal development and anxiety via the thyroid hormone receptors (TRs). The TRs are encoded by two different genes, TRα and TRβ. The loss of TRα1 is implicated in increased anxiety in males, possibly via a hippocampal increase in GABAergic activity. We compared both social behaviors and two underlying and related non-social behaviors, state anxiety and responses to acoustic and tactile startle in the gonadally intact TRα1 knockout (α1KO) and TRβ (βKO) male mice to their wild-type counterparts. For the first time, we show an opposing effect of the two TR isoforms, TRα1 and TRβ, in the regulation of state anxiety, with α1 knockout animals (α1KO) showing higher levels of anxiety and βKO males showing less anxiety compared to respective wild-type mice. At odds with the increased anxiety in non-social environments, α1KO males also show lower levels of responsiveness to acoustic and tactile startle stimuli. Consistent with the data that T4 is inhibitory to lordosis in female mice, we show subtly increased sex behavior in α1KO male mice. These behaviors support the idea that TRα1 could be inhibitory to ERα driven transcription that ultimately impacts ERα driven behaviors such as lordosis. The behavioral phenotypes point to novel roles for the TRs, particularly in non-social behaviors such as state anxiety and startle.
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影响因子：
3.5
作者：
Churchland, Patricia S.;Winkielman, Piotr
通讯作者：
Winkielman, Piotr
DOI：
10.1073/pnas.93.22.12581
发表时间：
1996-10-29
影响因子：
11.1
作者：
Dellovade, TL;Zhu, YS;Pfaff, DW
通讯作者：
Pfaff, DW
影响因子：
4.8
作者：
CARLSON, DJ;STRAIT, KA;OPPENHEIMER, JH
通讯作者：
OPPENHEIMER, JH
影响因子：
7.4
作者：
Hubbard, Catherine S.;Ornitz, Edward;Naliboff, Bruce D.
通讯作者：
Naliboff, Bruce D.
影响因子：
6.6
作者：
Bernal, J;Guadaño-Ferraz, A;Morte, B
通讯作者：
Morte, B